A Chemist's Laboratory Notebook

Free Radicals

2009-07-14T14:39:00.005-05:00

(Translation: Free radicals are everywhere...)
This is my daily weather website. For the past month or so, the advertisement at the top of page has been for Zellschutz (translation: cell protection) pills. According to the manufacturer's website, they contain a protective mixture of vitamins C and E, coenzyme Q10, selenium, and natural extracts from pomegranate, grapefruit, and green tea. Can antioxidants prolong your life and offer "cellular protection"? I think the verdict is still out on that.

But I do think it's funny that they've made the free radicals look like scary little bugs...They kind of look like bacteria (maybe), but certainly not free radicals...

Condensed Print

2009-07-06T14:24:00.002-05:00

Starting this month, the printed version of ACS journals will appear in a new condensed-print format. Apparently the print-based journals are no longer in high demand (print subscriptions down 50% in just 2 years is quite a loss), so to save costs, they will be printing 4 columns of text on just one page. From the image on the website, it looks like the articles will be printed in “landscape” format, with the page turned 90 degrees and shrunken in size.

I don’t know about everyone else, but I am a big fan of real paper issues of journals. It is nice to just sit down with the newest issue of any journal and flip through the pages, stopping if something catches my eye. Sometimes I end up reading some really interesting (and off-topic) research that way. You can’t just flip through the electronic version like that. Sure, if I’m looking for a particular compound or searching for a synthesis, I prefer the electronic version. Yes, I agree that there are MANY benefits to the electronic version of any journal. But, those rare times when I have a bit of free time and the geek in me actually wants to read about chemistry, I’d rather sit down at my desk and flip through the paper version. If I need to squint and get out my magnifying glass just to read the articles, I won’t be able to enjoy that time any more.

They try to make this sound better by saying that the new format is environmentally friendly. (Factoid: an annual subscription to all ACS journals weighs more than ½ ton!) I do like the idea of saving the environment (don’t get me started), but I don’t really know that a condensed-format journal is the way to go. If they really wanted to promote long-term sustainability, they would eliminate the print version of the journal completely.

Maybe I’m a little old fashioned, but I’m sad that paper is going out of style.

(After a quick search, I also found this article on the Chemistry Blog about condensed print).

Happy Birthday...kind of...

2009-07-01T15:00:00.006-05:00

Well, it's not exactly my birthday, but it is my 1-year Ph.D. birthday, and that is certainly worth writing about! It is really difficult to believe that one year ago around this time I was out celebrating the new title and enjoying every second of it. Other than my wedding day, the day of my final defense was one of the most memorable of my life.

So what has changed in the last year? Other than my new job in a new country, not much. Well, I guess there is a new addition to the family...

...but you can see he fits right in.

Hopefully now that I've settled into my new job, I will have a little more time to write here once again.

2008-06-14T18:58:00.004-05:00

This is your desk:

This is your desk in grad school:

This is your desk in grad school 2 weeks before your final defense:

Periodic Table of Fruits and Nuts and Periodic Table of Vegetables

2008-06-09T12:42:00.002-05:00

Does it make me a big dork because I want the Periodic Table of Vegetables for my new kitchen? The Periodic Table of Fruits and Nuts is pretty nice too...

Plants and your health...

2008-05-29T19:27:00.005-05:00

It's getting to be the time of year when I like to start putting all of my plants outside on the balcony. Usually I also like to plant a couple of windowboxes full of petunias. Add a couple of tomato plants, and I am set for the summer. This year though, with my final defense set for July 1 (GASP!), I don't have time for any of this "enjoying the sun" nonsense. Instead I'm limited to reading here about plants that are good for your heath.

Who ever thought that my spider plant could be cancel out the effects of the formaldehyde potentially found in my clothes?

Or that a gerbera daisy could protect me from the benzene in inks?

Not sure about the accuracy of these statements (I'd love to know their sources), but it is cool to think that my overabundance of plants (more than 20 in 600 sq. feet) is good for something other than just improving my mood.

Legal problems of Ph.D's in Germany

2008-03-15T10:00:00.002-06:00

As some of you may know already, my husband is German, so what I read last night in C&EN (don't you think it is ridiculous that I often don't get C&EN until Friday?) really shocked me. Apparently some internationally-trained (non-EU) scientists in Germany are facing charges for using the title "Dr." on their websites and business cards. Before I started reading, I was sure that it must be something to do with the fact that the "Dr." title might be confused with a medical doctor in a foreign country. But as I read further, I realized this wasn't the case. According to Spiegel, this law stems from 1939--and in simplified terms states that foreign degrees are suspicious, and need to be verified. In those times, such a law might have made sense, but now it just seems outdated. Luckily, the German government has already started to fix things up; at a conference in Berlin last week (see point 5) it was decided that an American Ph.D's can use the "Dr." prefix in Germany as long as their degree was granted from an institution recognized by the Carnegie Foundation for the Advancement of Teaching.

Happy Pi Day!

2008-03-14T19:38:00.001-06:00

This video is kind of freaky, but it fits the pi day theme nicely. Enjoy!

New Bacteria isolated....from hairspray

2008-03-10T19:57:00.002-06:00

Earlier today when I read the news online, I came across this article. Basically, researchers in Japan have discovered a new type of bacteria. And it lives in hairspray. Of course, I had to look up the original article, and I just want to know why researchers decided to search for "hairspray bacteria" in the first place. Of course I've heard of various cosmetic products becoming contaminated with bacteria, and I know that many bacterial species are thermophiles, acidophiles, or even both, but I just didn't think that hairspray would be such a great environment. The newest ingredient in your hairspray bottle is from the genus Microbacterium and researchers have proposed the name Microbacterium hatanonis (in honor of the scientist Kazunori Hatano, a Microbacterium expert). For those interested, the rod-shaped Microbacterium hatanonis is aerobic and Gram-positive.

On a side note, when I first read the article and saw the words "parsimony analysis," I had to laugh, because my brain could only think of the Parselmouths (the characters in the Harry Potter books that can speak the language of snakes). In reality, parsimony refers to the idea that "less is more," or that the simplest explanation for something is generally the best. In this paper, maximum parsimony analysis was carried out to create phylogenetic trees demonstrating the relationship between the new hairspray bacteria and other strains of Microbacterium.

Answers Research Journal?

2008-02-28T20:26:00.004-06:00

First, I want to say I went to the Answers Research Journal website with a totally open mind. While I am not overly religious, I don't necessarily believe that science is at odds with religion. As an undergraduate I took a excellent class (I forget the name, it was something along the lines of "Great Issues in Science") and was first introduced to the writings of Paul Davies, Richard Dawkins, and Stephen Jay Gould. My favorite two "textbooks" from the class were "The Mind of God: The Scientific Basis for a Rational World," and "Origins: Cosmos, Earth and Mankind." If you are at all interested in science and/or religion and how the two subjects can come to terms with each other, I highly recommend these books as a place to start.

Anyways, when my husband sent me a link to ARJ last week, I was intrigued. It seems as if the journal is an offshoot of the website AnswersinGenesis.org. According to their website, "ARJ is a professional, peer-reviewed technical journal for the publication of interdisciplinary scientific and other relevant research from the perspective of the recent Creation and the global Flood within a biblical framework." At first I had high hopes (I mean, it is "peer-reviewed and everything, that must count for something, right?) and was really hoping for some cool science or interesting theories on how (Christian) religion and science can really go hand in hand. Andrew Snelling, the editor, certainly has the scientific credentials (a Ph.D. in geology from the University of Sydney) necessary for making informed scientific decisions.

So what did I find? Well, I only looked at the current issue, but I wasn't very impressed. Of the five articles, two were written by scientists from "Answers in Genesis" and one was written by a guy whose only credentials are his (home?) address. Two are also written in the first person (which in my opinion just doesn't work for scientific publications), and sound like sermons rather than peer-reviewed scientific research. I do have to admit, the article on Louis Pasteur is pretty interesting, and while I would classify this article on granite formation as opinion rather than research, it was entertaining (I hesitate to say informative) as well. Although I had high hopes and an open mind, I was really left a little disappointed at the end of it all.

Face Research

2008-02-25T21:39:00.002-06:00

This is not chemistry related, but I thought it was too cool to pass up. The Face Research Laboratory is run by Lisa DeBruine and Ben Jones, two experimental psychologists currently working at the University of Aberdeen in Scotland. I think the face average is the coolest part of the website, but you can participate in one of their many studies here.

Nature Chemistry

2008-02-25T21:26:00.002-06:00

Today over at the Sceptical Chymist, Stuart Cantrill revealed a preview of the Nature Chemistry website. The journal is set to open in April 2009. I must say I'm quite pleased with the color choice--the beautiful blue/violet color reminds me of the natural product analogs that one of my labmates is busy synthesizing.

Cheddar anyone?

2008-02-14T20:32:00.005-06:00

Why in the world would someone want to calculate the heat capacity of cheese? While I do enjoy a nice creamy Brie, fresh mozzarella (especially with tomatoes and fresh basil), and maybe once in a great while a strong stinky cheese (reminiscent of Limburger) that I tasted on the Azores, calculating the heat capacity of each individual cheese seems to be taking it a little far, doesn't it?

Apparently not. In order to design the perfect cooling systems for the food industry, it is important to know the heat capacity of the food you are dealing with. For cheese it seems like moisture content is key in heat capacity calculations. Formulas to calculate heat capacity for cheese tend to be more accurate for those cheeses with higher water content (soft cheeses). Who would have known?

Traditional Chinese Medicines as Modern Drugs?

2008-02-12T20:02:00.000-06:00

Earlier today I read an article entitled "How many traditional Chinese medicine components have been recognized by modern western medicine?..." in ChemMedChem. Actually, the title is what attracted me to this article. I've always been interested in alternative and/or natural medicine (maybe that comes with being a vegetarian?*), and really try to avoid taking unnecessary medicines (other than the occasional necessities like ibuprofen and when I was really sick this summer, I ended up taking hydrocodone and paracetamol--a.k.a. vicodin--followed by trimethobenzamide, both of which I resisted initially). In my kitchen I also have a tea for just about any ailment--lemon balm (melissenblaetter in German) tea will cure just about anything. While I've never actually tried any traditional Chinese medicines, a comparison of the components found in these traditionally used herbs and minerals seemed like it might be an interesting read.

Traditional Chinese medicine has been around for more than 4000 years and currently there are over 10,000 chemical components that have been extracted from almost 5,000 traditionally used Chinese herbs/minteals/animals found in the database of traditional Chinese medicines. Compared to Western medicine, this is pretty amazing. Synthetic drugs have only been around for about 100 years, and in one comprehensive medicinal chemistry database you can find about 8000 different molecules that have been approved for use as approved drugs. About 50% of these approved drugs are actually derived from natural products, so a logical conclusion is that there might be some striking similarities between the chemical components of traditional Chinese medicines and modern Western drugs.

According to the Zhang group, there are 327 compounds found in both the traditional Chinese and Western drug databases, and approximately 900 chemicals that are structurally similar (>85% similarity) between the two. Not surprisingly, more than a hundred of the traditionally used Chinese remedies display the same pharmacological effects as their corresponding Western drug. The pharmacological effects of many of the natural herbs were recorded in ancient Chinese texts dating back to the Eastern Han dynasty (~25 AD to 220 AD). For instance, among the 12 chemical components of the herb Coptidis rhizoma (used to treat gastric conditions in traditional Chinese remedies) are berberine, columbamine, coptisine, jatrorrhizine and palmatine. Today calystigine/palmatine is known as an antibiotic, and a structurally similar compound called berberine is believed to be an inhibitor of Helicobacter pylori.

The article also stresses the potential that traditional Chinese medicines could have in drug discovery efforts, in particular in finding multicomponent therapeutics that combine two or more active ingredients into one single dose to hit several targets at once. The herbs used in traditional Chinese medicine can easily have over 50 chemical components. Although each single component might not be active, in combination they might be able to potentiate the effects of other chemical components, or they might work in combination to produce unexpected results. Additionally, traditional Chinese medicines are often prescribed in combinations. Would it be possible to combine the well established formulae of traditional Chinese medicines with Western medicine to produce combinations of drugs with lower risks of adverse drug-drug interactions? Now that we know traditional Chinese medicine has somewhat of a scientific basis, hopefully more work will be completed in this area. Acupuncture has already gained acceptance in many Western societies, so maybe this is the wave of the future.

*My cat on the other hand, certainly isn't a vegetarian. In addition to lounging in the sun on his new window seat, he enjoys his dinner of duck and peas very much.

Sciencedebate 2008

2008-02-02T11:28:00.000-06:00

I haven't checked out the entire website yet, but this seems like a good idea. While there are certainly other important issues, why not encourage a presidential debate on science and technology? Several thousand scientifically minded individuals and organizations have already signed, including the American Association for the Advancement of Science (AAAS), Sigma Xi, Roald Hoffmann (Nobel Laureate), Robert Grubbs (Nobel Laureate), Richard Schrock (Nobel Laureate), Peter Agre (Nobel Laureate), Phillip Campbell (editor of Nature), and Rudy Baum (editor of Chemical and Engineering News).

(thanks to Mirth)

Nanocoils

2008-01-30T21:59:00.001-06:00

My husband works in what I consider to be the materials side of chemistry (he is currently the only chemist in a group of physicists), so even though I am an organic chemist at heart, I really enjoy reading about new developments in nanotechnology. Yesterday I came across a paper entitled "Conductive One-Handed Nanocoils by Coassembly of Hexabenzocoronenes..." and I actually thought it was pretty interesting. Coiled nanofibers have been made previously, but little is known about their conducting properties. This is mostly due to the fact that coiled assemblies of aromatic molecules are not overwhelmingly stable. If one could create coiled, single-handed, electroconductive nanostructures that were also stable, it would be possible to create tiny little electromagnets. Cool, huh?

Hexabenzocoronene (HBC) with alkyl and triethylene glycol substituents can self assemble into nanotubes; appending norbornene groups at the end of the triethylene glycol chains leads to the formation of both right- and left-handed helical nanocoils upon self assembly (1). While these nanocoils can be stabilized by subsequent ring-opening methathesis polymerizatio n (ROMP) of the norbornene groups, they are actually only the kinetic product of self assembly. Without the ROMP stabilization, they are eventually converted into the more thermodynamically stable nanotubes. This all seems fascinating enough, but members of the Aida lab were able to take things a step further using what they call the "sergeant and soldier effect" to control the formation of left- or right-handed nanocoils. Doping the original HBC/norbornene construct (1) with as little as 20% of HBC with a shortened linker containing a chiral handle (either R or S) produced single-handed coils (S enantiomer --> left-handed coils, R-enantiomer --> right-handed coils). After doping with I₂, the coils are also conductive. It only takes a few sergeants to control an army!

Periodic Table of Sentiments

2008-01-27T18:40:00.000-06:00

While elements like ¹⁸Is (I'm sorry) and ⁴⁹Ty (Thank you) are certainly made up, I think that any chemist would get a chuckle out of receiving one of these lovely periodic table of sentiments cards from Pink Loves Brown...

Chemistry on TV...

2008-01-20T18:52:00.000-06:00

Today when I looked in the newspaper, I just happened to see an advertisement for this new show on AMC. I was so happy that both bromine and barium were pictured with the correct atomic number. Yay for the proper use of chemistry in the media!! Since I don't have cable, I won't be watching tonight, but from some of the pictures online, it seems that at least some chemistry might actually appear in the first episode. Bunsen burners, Erlenmeyer flasks, electron configurations, all that good stuff. Unfortunately safety doesn't seem to be a high priority. In the first picture, the high school chemistry teacher on "Breaking Bad" is shown in front of a flaming Bunsen burner without goggles. But I forgive them this time, as I did enjoy this quote from the show's blog: "Electrons change their energy levels. Molecules change their bonds. Elements combine and change into compounds. But that's all of life, right? It's the constant, it's the cycle." Yes, chemistry is life.

PCR, when you need to find out who the daddy is...

2008-01-11T21:48:00.000-06:00

A biologist in my lab sent this out yesterday. It's from the Biorad website and only gets better the longer you listen. Enjoy.

Priceless...

2008-01-08T18:46:00.000-06:00

My husband made a nice little visual aid to go along with the post from yesterday...

How much are you worth?

2008-01-07T19:06:00.000-06:00

Some recent information to absorb (all rounded to the nearest thousand):

An average graduate student in the chemical sciences earns per year before taxes: $22,000 (wow, do i really get paid that much? it doesn't feel like it.)

Tuition paid per year on behalf of the graduate student: $12,000

Facilities and overhead paid per year on behalf of the graduate student: $13,000

Misc. expenses paid on behalf of the graduate student ("fringe"): $1,000

Being told that an average Ph.D. (assuming a full five year service) costs more than a quarter of a million dollars: PRICELESS

10 commandments for keeping a lab notebook

2007-12-31T20:09:00.000-06:00

Another list, just in time for the new year! My boss recently reminded us what it takes to keep a proper lab notebook, and I wanted to share it with you.

Here is the list:

1) Reference for the reaction (from the literature or from one of your or another lab member's lab notebook, for instance Amanda's Notebook VI, page 228)

2) Structure of reactants and expected products

3) Table with mgs/mmols/equivalents/densities/origins of reagents. That last one is really important. If you used a mysterious, old reagent that has been sitting on the shelf for 20+ years and got great results, when you buy a brand new bottle and don't get similar results, you have a reason. The impurities in reagent that is 99% from Sigma might not be exactly the same as a 95% reagent from a different supplier. Also, write down where you found the reagent. I don't know about your lab, but mine has about 10 different fridges/freezers, and sometimes it is difficult to remember exactly where you put something.

4) Reaction procedure--we all already do this, right?

5) How did you monitor the reaction? Draw your TLC or attach your HPLC trace.

6) Workup procedure--sometimes I get a little lazy here.

7) Purification procedure. Include the size of column, amount of silica used, etc.

8) Results. mgs of product obtained, % yield, and physical state of material -- bright orange powdery solid, 239 mg, 98% yield

9) Characterization of products. Include reference to your NMR (if you keep electronic copies, write down the filename!) and explain. For instance, 13C NMR (Amanda_VI_228b_pure), for spot at 0.6 Rf (1:1 EtOAc:Hexanes) consistent with expected product X.

10) Don't forget to write down the date!

And as a general rule, try to write down things within 24 hours of completing them. You tend to forget things if you wait too long.

Anyone have anything to add to this list? While I generally know what to put in my chemistry lab notebook, I must say that I don't necessarily include all of these things every single time. Maybe that will be one of my resolutions for 2008. On a similar note, I also tend to do quite a bit of biology. Do any biologists out there have any suggestions for what to include in a biology lab notebook?

10 Simple Rules for Graduate Students

2007-12-15T17:27:00.000-06:00

One of the professors here recently sent around an article with advice for graduate students. As I'm already in my 5th year here, many of the 10 simple rules aren't so relevant for me any more, but I wanted to pass them along anyways.

A short summary--

1. Let passion drive you.
You had better be excited about the project to which you are going to dedicate the next 5+ years of your life. If you don't like reading and thinking about it now, it probably won't grow on you. And those crazy experiments that come to you in the middle of the night? Go into lab the next day and try them out, because you never know what might work.

2. Select the right mentor, project and laboratory.
Mentor: It's this simple: pick a mentor that you can get along with in a professional atmosphere. Young or old, male or female, it doesn't really matter as long as you respect him/her and can understand his/her expectations of you.
Project: It is very painful to fail again and again for months at a time. Sure, it builds character, but that doesn't make it any easier. Make sure to talk with group members and find out the inside scoop as to what projects seem to have a lot of potential at the moment.
Lab: Work with people you like or at least those you can stand to be around for 10+ hours a day, 6+ days a week. If you can't talk with your lab members at least in a work related fashion, you really are going to be struggling when it comes time to ask for help.

3. Be an independent thinker.
It is okay to disagree with your PI on a scientific hypothesis, as it will only make both of you stronger. Just make sure you have all the data to back yourself up.

4. Balance is a necessary part of life.
Go to the gym, plan movie nights on the weekends, make group dinners. Some of the best friends that I have made during graduate school are the ones that I met biking 30 miles one or two times each week. Although the field of chemistry is relatively large, the people you meet and work with now will be your peers/reviewers/interviewers in the future. It is good to have friends in the field.

5. Think ahead to your career.
Take advantage of everything your school has to offer. Take extra classes if you want. Try to have as many different experiences as possible so that you know what you would like to do when it comes time to look for a job.

6. Remain focused on your hypothesis, but don't let it take over your life.
Set up experiments to prove your hypothesis, but set up just as many to disprove it. Don't forget the big picture. Sometimes proving that a theory is wrong is just as important as showing that it is right.

7. Fix problems now.
If you are struggling with some aspect of research or graduate school, talk to someone before it gets to be a big issue.

8. Publish! Attend meetings!
Other scientists may reveal tidbits of information at small meetings that they might not otherwise discuss in the literature. Often times these little things are the key to your success.

9. Be confident (but not arrogant), be thick skinned.
At some point your committee, group or class will question you until you feel like crying. More than likely this will happen multiple times. This is normal and hopefully will help you build confidence. Over prepare for everything.

10. Pick your thesis committee wisely. Stay in contact with them throughout your time in graduate school.
These will be the people writing your recommendation letters. Make sure they know when you make significant progress. Email them your most recent papers and set up meetings with each committee member at least once each year.

3-D Sugar Printer

2007-12-13T22:09:00.000-06:00

Well, the people at Evil Mad Scientist Lab-
oratories have come up with something pretty sweet--a 3-D sugar printer. I have always thought that three dimensional printers are very cool and I even remember the first time that I even learned that they exist--on my tour of the Beckman Institute at University of Illinois.

The basic concept of the 3-D sugar printer follows standard solid freeform fabrication techniques. Simple two dimensional layers are stacked on top of each other to form a more complex 3-D form. So how do the Evil Mad Scientists do this with sugar? First, a layer of low melting "granular printing media" (sugar) is placed on a flat surface. By applying a technique called selective hot air sintering and melting, a burst of hot air is applied to the sugar in preselected locations. As the sugar melts, it fuses together with other sugar grains and eventually a two dimensional image appears. Next, the flat surface is lowered slightly and a second layer of sugar is sprinkled on top. Again hot air from a heat gun is applied to the surface in preselected locations. This time the new two dimensional image that is formed is also attached to any overlapping fused spots in the underneath layer. Repeating this process over and over again eventually yields a three dimensional object made completely out of sugar!

The inventors claim that their production process is very similar to selective laser sintering (SLS), but at a fraction of the cost. SLS is commonly utilized in manufacturing and uses a very expensive high power CO₂ laser (thousands of dollars), whereas the Evil Mad Scientists' technology only needs hot air from a $10 heating element.

If you are really interested, you can visit the CandyFab project, which has all the information you need to build one of these machines at home for yourself. Now I'm hungry--anyone up for some caramelized almonds?

Atomium

2007-11-27T19:00:00.000-06:00

On one of the bulletin boards outside of our labs someone recently posted a brochure about the Atomium, and it really caught my attention. This interesting-looking building was erected for the International Exhibition of Brussels in 1958 (the World Fair in Brussels). Based on the structure of solid iron (which by the way is body centered cubic) magnified 165 billion times, the Atomium was designed to "embody the audacity of an epoch that seeks to confront the destiny of man with scientific discovery." Though I don't believe the individual spheres of the building are 165 billion times bigger than a real life iron atom (an iron atom is approximately 2.5 Angstroms in diameter x 165,000,000,000 = 135 feet, and the actual building spheres are only about half that size), the distances between the atoms are supposedly magnified to that size.

Visitors are only allowed in 5 of the 9 spheres--the base (Henri Storck sphere), where you will find an exhibit dedicated to the 1950's, the top restaurant sphere, the central (Waterkeyn) snack bar sphere, the sphere named after the Belgian artist Marcel Broodthaers, and the children's only sphere. At 115 feet long, the escalators found inside the tubes of the Atomium are some of the the longest in Europe.

Why make a body centered cubic building modeled after the structure of iron?? It was a tribute to the steel companies that helped to sponsor the construction by providing raw materials.

After seeing these pictures, I really want to visit. Thanks to Mirth (and her family) for the lovely photographs.

Stairs connecting the spheres:

A view to the outside

Artwork inside of the Atomium

Motivation

2007-11-21T20:14:00.000-06:00

How does your boss motivate you?

Survey by Quibblo

Cockroach behavior

2007-11-20T17:48:00.000-06:00

There is quite a cockroach infestation in our chemistry building here (although come to think of it, I haven't seen any bugs in at least 6 months, hmmm...), so I was naturally curious when I came across this paper in Science. For a second think back to all of those science fiction movies you watched as a kid (and you probably have seen at least a few if you are a scientist), especially the movies involving robots--in particular robots that were integrated into human society and took on some seemingly human emotions (R2D2 and 3CPO from Star Wars are my all time favorite robots)...Now think about the social integration of robots on a slightly smaller scale (with insects), and that is exactly what José Halloy and coworkers have accomplished.

American cockroaches typically recognize chemical cues from their neighboring cockroach friends, and utilize these signals to act as a group and make self-organized choices. Self organization complements the preexisting environmental signals and coexists with status levels between the insects such as leader/worker relationships. Halloy and coworkers claim to have socially integrated cockroach-sized robots into a cockroach collective. How was this achieved? You guessed correctly--through chemistry! Basically by extracting and characterizing the hydrocarbons found in the cockroaches' exoskeleton, researchers identified compounds that were key in inter-cockroach recognition. By coating the robots in these extracts (which included compounds such as 6,9-heptacosadiene and 3-methylpentacosane), cockroaches accepted these robots and, even more amazingly, allowed the robots to influence decisions made by the cockroach community.

My only question is who got to perform the extraction of the cockroach exoskeleton into dichloromethane? That just sounds pretty icky to me.

Ham Flavor?

2007-11-13T19:59:00.001-06:00

When I think about all of the artificial flavorings that go into foods, it always makes me feel a little disgusted. Sometimes even the so-called "natural" ingredients creep me out, so I really hate to think what might go in this soda to make it taste like ham. But I do give them credit for a cool (yet slightly disgusting) idea.

For your enjoyment, I've compiled a short list of the some of the more common flavoring molecules below.

Flu Vaccine and Thiomersal...

2007-11-07T19:29:00.001-06:00

Today I got a flu shot. In my past life, I used to consider people who got such unnecessary vaccinations as "weak," but now I just figure, why not? Who wants to deal with a bad case of the flu, miss work, and possibly end up in the hospital (as I did this summer with a severe case of the stomach flu)? Of course the vaccine doesn't catch all strains of the flu, but hopefully it will at least give me some protection, which is certainly worth suffering through one day with a sore arm.

As I was signing my life away while waiting for the shot (no, I won't sue the school if I have an adverse reaction to the ingredients of the vaccine), the information packet warned that this shot contains thiomersal and that people with known allergies to this preservative should not be getting the shot. We have all heard about the controversy assocaited with vaccines; one side believes that some vaccines might cause autism and other disorders associated with brain development, while the other side does not believe this to be the case. Thiomersal is at the center of this debate.

Looking at its structure, it is easy to see why this compound might be considered suspicious. While it is a powerful preservative because of its antifungal and antiseptic properties, it also is an ORGANOMERCURY compound. Basically one of the reagents that I wouldn't like to work with in lab. You only have to read the story of Prof. Karen Wetterhahn (which was posted for some time in our group's hallway as one of those 'be more careful in lab' warnings) to know why I might refuse to work with alkyl mercury compounds. Basically the harmless sounding name thiomersal actually refers to a compound that probably breaks down to ethyl mercury inside of your body. At the same time, it is a necessary part of the vaccine and works to prevent possible adverse side effects like as bacterial infection that might occur in vaccines lacking preservatives. And is ethyl mercury just as bad as methyl mercury? Apparently not [1], but that doesn't stop parents from worrying about their children.

Personally, I wouldn't be too worried about thiomersal containing vaccines. In general, very few vaccines contain thiomersal any more, and those that do have extremely low levels present. Looking at this table, some vaccines contain 0.01% thiomersal. In studies, levels of thiomersal producing inorganic mercury levels ranging from 201 micrograms/Liter to 50 milligrams/L were shown to be toxic in cell culture, (and, for those interested, these levels induced activation of caspase-3). Levels of thiomersal used under normal vaccination conditions are much much lower. In the worst case scenario, after a complete series of vaccinations a very very small child would receive less than 50 micrograms of inorganic mercury per kg of body weight. Additionally, ethyl mercury (half life of about 18 days in the bloodstream) does not bioaccumulate like methyl mercury (half life of 50 days).

So go ahead and vaccinate your children. And why not get a nice flu shot for yourself while you are at it?

[1] How do I know ethyl mercury isn't near as toxic as methyl mercruy? Of course there have been some scientific studies completed on this very subject, but I also have some firsthand experience. Thiomersal was once sold as Merthiolate. I am not that old yet, but I still can remember back to when my dad would put this bright pink solution on any little cuts or scrapes that I would have. It always stung for a second, but nothing ever got infected. Strange to think that it was actually an ethyl mercury containing product. In 1998 the FDA banned the use of thiomersal in over the counter products, which explains why I haven't been able to find this wonder drug from my childhood in any stores.

Which one of these is not like the others?

2007-10-31T17:26:00.000-06:00

I finally got a picture from the East Coast PARP Conference that I attended way back at the beginning of October. Other than the obvious difference of being the only female non-faculty presenter (speakers are in the front row), I am pretty sure that I was the only chemist there!

Tattoo Chemistry

2007-10-29T20:04:00.001-06:00

After I recently read a book about about words on skin, I jokingly told my husband that I wanted to get a tattoo. Now we both know that the likeliness of that is about 0.1% (firstly, needles are one of my least favorite things, and even working with them in lab sometimes gives me chills, and second I can't stand seeing blood, particularly my own), but I must have worried him somewhat, because the he gave me the September issue of "Nachrichten aus der Chemie" (kind of a German version of C&EN News, but not quite) that contains an article on tattoos. Other people have written about it--Carbon Based Curiosities comes to mind--but I hadn't really ever seen the actual structures of tattoo pigments, so it was actually quite an interesting read.

In the past, inorganic pigments such as titanium dioxide (white), cadmium sulfide (yellow) and iron oxide (black) were used as pigments. These compounds are relatively insoluble and thus produce long lasting color. Today organic compounds make up the bulk of colored tattoo pigments, while totally black tattoos are still made out of carbon black which unfortunately contains toxic impurities associated with its production. I've drawn out some of the structures of common organic tattoo pigments for you to see; most of the structures contain polycyclic azoles, which I guess isn't very surprising.

Not to scare anyone away from getting an awesome tattoo of their favorite natural product, but the bulk of the article is dedicated to the dangers associated with tattooing. Amazingly, some pigments that aren't allowed in cosmetics due to toxicity are still used in tattoos (at least in Germany, and I wouldn't be surprised if the same is true for the United States). Also, there are many dangers associated with the breakdown products of the pigments that are utilized, especially in the case of red pigments. One can imagine that these decomposition products could be oxidized in the body to produce an even larger number of unknown chemicals that could potentially be hazardous to you health. But don't let any of that stop you from getting that tattoo of the periodic table on your arm like you've always wanted--tattoos can't be any worse for your heath than washing your hands in benzene (which from what I hear was a relatively common practice for chemists 50 years ago).

Cool toaster...

2007-10-25T22:25:00.001-05:00

Not exactly related to chemistry, but I just read about this toaster on infektia.net and I think it is really cool. Sasha Tseng, a Japanese designer, came up with the concept of the toast messenger to make your meals a little more interactive. Basically you write a little note on the screen and then it can be toasted into your bread (or whatever you prefer to eat) OR a little printer (with jelly as an ink of course) can squirt out a color message. Neat. Now you can draw molecules on your toast!

Ego boost

2007-10-24T19:46:00.000-05:00

Well, I've finished 2/3 of my North American speaking tour (as my boss likes to call it), and it is actually nice to spend some time in lab after all of that traveling. I do enjoy visiting new places quite a bit though, almost as much as I enjoy giving seminars. No, I am not being facetious--under the right conditions I actually enjoy public speaking. As long as I have had a chance to prepare and am interested in the subject (in this case, my research), it is kind of fun to watch an audience respond and react to what I am saying. Anyways, my PI got an interesting email after I had returned from one of of my speaking events. The general gist of the is shown below, with my comments shown in italics:

"Mr. H...(my boss who is most certainly deserving of a Prof. or at least a Dr. in front of his name),

I did not found the email address of A (referring to me)... who gave remarkably interesting talk regarding enzyme Y (go me!!!)....Can you please forward this email to Dr. N (once again, referring to me)? We are very excited about the possibility of a collaboration....

Regards,
X (eager grad student who got some details a little mixed up)"

Luckily my PI has a good sense of humor, and we joked about the whole thing.....It is kind of fun when someone thinks that you are deserving of a "Dr." title when you don't actually have one yet.

But don't worry, I'm not letting it go to my head.

"Girl Chemist"

2007-10-10T13:07:00.000-05:00

Walking down the hall earlier today, I noticed that one of my labmates had posted an interesting article near her door. Taken out of a Science Illustrated (no, not Sports Illustrated) issue from 1949, the article entitled "Girl Chemist" made me stop in my tracks and take a look. Of course if the photos don't make you laugh (no goggles, gloves, labcoats, eating lunch right off the bench, etc.) the text certainly will. "Chemistry, once strictly a man’s profession, has become increasingly hospitable to women" Hmmm, from the title "Girl Chemist" I wouldn't have thought that. If the point of the article was to show that women can do chemistry too, wouldn't "Female Chemist" or "Woman Chemist" have been more appropriate?

And it goes on..."At 22. Jackie Bates has made chemistry her career. Although it is a lonely, tense, exacting, sometimes frustrating profession, she enjoys it. She finds her work satisfying, her day full, her advancement altogether satisfactory. After 18 months on the job she regards herself as a veteran: 'The sulphur dioxide smell doesn’t bother me any more.'"

Taking a look at the chemistry section of Modern Mechanix, there are certainly a few other articles worth looking at. Some of them that I found particularly interesting--the very instructional "How to set up your chemistry laboratory, "Fun with explosive gases,"Thrilling stunts with a glass eating chemical,"Mercury the liquid metal," and last but not least "Chemcraft for victory". Enjoy.

Traveling...

2007-10-08T20:40:00.001-05:00

Do you ever have weeks (or months) where nothing seems to get done? Unfortunately, as much as I am trying, it feels like for the last few weeks my research has been on pause and nothing seems to move forward. Not a good thing for a student starting their 5th year. At the beginning of my grad school career I loved "slow" weeks, when I had the time to read/write/think. Now it makes me nervous not to have an experiment running, and I miss the fluttery feeling I get in my stomach when I am waiting for the results of an important NMR or biological assay to appear on the computer screen. Lately I've been chained to my desk, working on various presentations (3 different ones in all), writing, and reading. (Don't get me wrong, I also enjoy the quality time spent at my desk, but I do want to graduate in about a year, so I like to stay busy).

This past weekend I was at the East Coast PARP Conference in Quebec City. Not only attending, but holding a 40 minute seminar on my research. As sick as it sounds, I actually enjoy public speaking, but in this case it was particularly nerve-wracking. Imagine--I was the only non-professor presenting (except for the guy from NIH, but he doesn't count since he has a Ph.D. already) to an audience of experts on my particular subject. Also, I was the only female presenter. After my talk was finished (luckily I was the second speaker of the day), I was able to enjoy the meeting, learn about some awesome research, and meet all the "famous" people in my field. It's a good thing that I remembered a pen and paper despite my nervousness; I took over 20 pages of notes. While I was at the conference on Saturday, my husband got out and explored the old part of the city, so that he could serve as my tour guide on Sunday. Early October is the perfect time to visit Quebec--the leaves are at their peak and the weather is still relatively warm.

On Thursday I'm off to Michigan to visit my alma mater and once again give a little presentation, only this time my main audience is undergraduates--a huge difference from the conference this last weekend. The last of my seminars will be in the middle of November, and I keep telling myself if I can last until then everything will be smooth sailing.

I hadn't been to an airport in a few months, and was pretty surprised at some of the new security measures. Basically I had to enter a walk-through "portal," stop inside for about 20 seconds while puffs of air shot at me from all directions. It is pretty funny to watch people going through these machines for the first time--almost everyone that I watched go through jumped when the first puff hit them, and then gave a little shiver as they walked through the exit. After a little internet searching, I confirmed my suspicion that this little machine is just a glorified mass spectrometer. According to the Smiths website, the Ionscan Sentinel II (the machine at both airports that I went through this weekend) can detect almost any explosive (RDX, PETN, and TNT to name a few) as well as narcotics (Cocaine, Heroin, THC, and Ecstasy). For the few seconds that I was standing under the puffing air, I was thankful that I hadn't done any real chemistry in lab the last week. What would have happened if the "Sentinel" would have found traces of a NO₂-bearing compound on my shoes, hair or clothes?

Do chemists need special notes when we go through airports now?

Small molecules that modulate quorum sensing

2007-09-14T21:36:00.000-05:00

On Thursday Helen Blackwell from the University of Wisconsin Madison braved the cornfields and soybeans that pave the way south to the U of I and gave an awesome seminar. Unfortunately I didn't get to go out to lunch with her, but several other members of my group did. From what I hear, she is quiet, witty, observant, and very interested in hearing what students have to say. Although I was a little disappointed that she didn't mention much about her group's work on small molecule macroarrays, she did discuss their recent article on quorum sensing in Vibrio fischeri, which is a fascinating story for anybody interested in chemical biology. She even satisfied those hard-core organic chemists with some microwave assisted reactions. If I remember correctly, they have been able to reduce the reaction time from 24-48 hours to under 30 minutes for the final cyanogen bromide mediated cyclization step in the synthesis of N-phenylacetanoyl-L-homoserine lactones. Pretty amazing what microwaves can do.

Bacteria are able to control their population growth through a process called quorum sensing. By releasing certain molecules into their media, bacteria can signal to each other and thus are able to alter their mode of growth; essentially this communication allows them to function as muticellular communities rather than single celled organisms. Gram negative bacteria are known to use N-acylated-L-homoserine lactones (AHLs) for communication. Previous studies have shown that phenylacetanoyl-L-homoserine lactones (PHLs) can act as antagonists of quorum sensing, so Blackwell and coworkers created a small library of PHLs and tested their activity in the bioluminescent bacteria Vibrio fischeri. While this library contained less than 30 compounds, it included some of the best antagonists AND agonists of gram-negative bacteria that are known to date. Very small structural changes elicited huge differences in activity.

In my opinion, one of the most interesting points of the talk was Blackwell's discussion of the Hawaiian bobtail squid. Apparently its light organ (which is used for hunting and prevents the squid's shadow from alerting potential predators/prey to its position) is inoculated with V. fischeri shortly after birth. Quite an interesting symbiotic relationship--the squid provide the bacteria with a home and food source in exchange for light. Blackwell shared some preliminary data with us indicating that the superagonist discovered in the small PHL library is well tolerated and active in vivo. The juvenile squid utilized for these experiments are tiny enough to fit into the wells of a 96-well plate, and in my opinion they are very cute (as illustrated by the picture above, V. fischeri image from Geske, G.D. ; O’Neill, J.C.; Blackwell, H.E. (2007) ACS Chemical Biology 2(5), 315-320.).

Binding DB

2007-09-08T15:32:00.001-05:00

As brought to my attention by my PI--the Gilson lab at the University of Maryland Biotechnology Institute has been working to develop a database of known protein-ligand binding affinities, also known as the BindingDB. While the BindingDB currently contains only about 15,000 small molecule ligands and 30,000 affinities to proteins measured through isothermal titration calorimetry (ITC) and enzyme inhibition methods, the database is rapidly increasing in size, at a rate of about 10,000 new data points per year.

You can search for your favorite protein or ligand, but there are also several other search features such as molecular weight, K_i, and substructure. Users are encouraged to deposit data from their own published binding experiments, so hopefully this database will continue to grow in the future. Once enough information has been collected, I can imagine that the BindingDB will become a powerful tool in drug discovery--Not only can you download computer models of compounds and affinity measurements, but there is also an interesting virtual screening section of the website that I'd like to explore when I have some spare time.

Of course, this isn't the only database that characterizes molecular interactions. Some of the others include:

Ocean breeze...

2007-09-03T19:59:00.000-05:00

While I've always thought the smell of the ocean was quite a pleasant one, I'm apparently mistaken. According to Andrew Johnston and coworkers, dimethyl sulfide (DMS) is the major form of sulfur released from aquatic environments and contributes highly to the distinctive smell of the ocean. Honestly, I've smelled a bottle of DMS before and the thought of comparing its smell with that of a gentle sea breeze never crossed my mind. Production of DMS in the oceans stems from dimethylsulfoniopropionate (DMSP), which is a metabolite produced by seaweed phytoplankton, seaweed macroalge, and salt marsh grasses. During times of stress (like those times you come back from the beach looking worse than a lobster, when the UV-index is extremely high) plankton release DMSP, which is subsequently catabolized into DMS. One of cool fact--oxidation products of DMS are known to seed clouds--so do these creatures purposefully secrete DMSP to generate clouds and thus protect themselves from the sun's harmful rays? Something tells me that this is not the case, but it is interesting to consider nonetheless. DMS production protects cells from ROS and has been shown to prevent some kinds of viral infections in algae, and these are the more likely reasons for DMS synthesis. A potential downside of DMS production for these creatures?? They get eaten. Both crustaceans and birds are known to be attracted to its smell as it serves as a chemical indicator for food[1],[2],[3].

Note: Be sure to check out the "CLAW hypothesis" if you've never heard of it before...

Idea Generator

2007-09-03T19:25:00.000-05:00

Not related to chemistry, but worth the visit.

Moving on up...

2007-08-20T20:12:00.000-05:00

I have officially moved up in the world of graduate students. As of 4:00 this afternoon, I have an "undergrad" at my disposal!

Fire!

2007-08-17T19:54:00.001-05:00

Friday evening after work I popped a Lean Cuisine into my trusty Kenmore microwave, turned the time to 3 minutes, and went to check my email. After I heard a loud popping sound, I went back into the kitchen only to discover that my microwave had caught on fire. Tons of disgusting-smelling smoke filled the air, and I could barely see my kitchen. Luckily, I'm a chemist, so I was prepared to pull the trigger on the fire extinguisher. Amazingly, the chemistry microwave we have in lab has never created any problems, but my own food microwave decides to blow up in my face! My new cat and I ended up spending the night at the Ramada Inn to avoid inhaling the nasty smoke.

So I am wondering--do all of your chemistry departments offer safety training before you start working in the laboratory? We had to take a laughable online safety exam--but also had a small practical course in which we were required to put out a small fire using an extinguisher. Although I found it annoying at the time, I'm very grateful for that hot summer afternoon that we spent putting out fires. I had never used a fire extinguisher before in my life.

Won't you try some of this lovely lemonade?

2007-08-13T21:32:00.000-05:00

Where have I been? Well, among other things, I was getting shot up with iopromide and drinking a lovely lemon-flavored mixture of 2% barium sulfate. (If I hadn't sick already, that concoction would certainly have done the job). While barium is a toxic metal (atomic number 56, which makes it perfect for CT scans because it readily absorbs X-rays), barium sulfate has a very low aqueous solubility and is quickly flushed out of the body, thus preventing any extremely bad side effects. (On a sidenote, barium carbonate, which is soluble in stomach acid, is toxic and used as a rat poison). When I mentioned to the CT technician that I am a chemist, he was super nice and even showed me the drug data sheet on iopromide (which even had a structure!), so I could get a glimpse of the lovely iodinated compound that would soon be running through my body. As far as I can tell, iopromide was developed in the early 1980s and is one of the safest nonionic contrast agents out there. Nonetheless, it is necessary to sign an "informed consent" form before the drug can be administered. With an iodine content of almost 50%, iopromide is able to enhance the visibility of organs and blood vessels during radiographic procedures. Once it is injected, it feels like you are on fire and you get a yucky taste in your mouth, similar to the one you had in 1st grade when you licked the flagpole :o)

Mosquitos and cat(nip)...

2007-07-29T18:50:00.000-05:00

Earlier this month I was quite confused. Although we are in the prime of summer--hot and humid Illinois weather--I hadn't gotten a single mosquito bite. Unfortunately I had that thought a little too soon. Last weekend when I awoke on Saturday morning I was covered in tiny red welts, evidence that my screen windows just aren't doing their job and that the little vampires had attacked me in the night. So what chemicals can help to keep away these pesky insects?

DEET, or meta-N,N-diethyl toluamide, is one of the most common mosquito repellents that I have seen used in the United States. While I haven't read any complete studies describing exactly how DEET works, it is believed that this molecule somehow binds to female mosquito sensory receptors (on a sidenote, generally it is only the female mosquitos that practice hematophagy, as they require extra protein in order to reproduce) and prevents them from recognizing some of the chemicals excreted by the human body, especially lactic acid and carbon dioxide. Inhibition of these receptors leaves the mosquito circling in confusion and allows us to enjoy itch-free summer evenings by the lake. DEET does have some unpleasant side effects; it can damage many synthetic fibers (though leaves cotton and many natural fibers untouched) and has long been known to have negative-side effects in aquatic life. Additionally, studies published in the Journal of Toxicology and Environmental Health and Experimental Neurology by Mohamed Abou-Donia and coworkers have shown that prolonged use of DEET in rats can cause neurodegeneration, particularly in the cerebral cortex, the cerebellum, and the hippocampus [1], [2].

In Europe Icaridin / Picaridin is a common insect repellent, and some studies have shown that its activity is similar to that of DEET, but without any of the toxic side effects. Of course we all have heard of "natural" alternatives to these compounds, including citronella, beautyberry, geranium, lemon and eucalyptus oils, but did you know that catnip^* (nepetalactone) has also been promoted as a "chemical free" means of eliminating mosquito bites [3], [4]? Interesting how the word chemical is generally considered taboo when promoting a new product; nepetalactone sure looks like an organic chemical to me!

If you are interested, the University of Florida has complied a list of several commonly available insect repellents with their effectiveness here.

^*At the risk of sounding like carbon based curiosities, I just had to include some kind of reference to cats in this post. Last week I adopted a wonderful tabby! Isn't he cute?

Semisonic - Chemistry

2007-07-20T19:57:00.001-05:00

Because it is Friday...

Maiglöckchen

2007-07-18T18:36:00.000-05:00

Well, I seem to be having some sort of internet connection problems at home, thus the lack of posts of late. It is very frustrating to pay for something and then not have it work, don't you agree?

Yesterday I was once again allowed to "play" with the confocal microscope; actually this was the second of my training sessions (for a total of 4 hours), so now I'm kind of an expert (not really) and allowed to use it on my own. Certainly I'm not close to being a know-it-all with the confocal scope, but it is nice to be able to make the judgment between just a pretty image and an accurate representation of what is on the microscope slide. I was quite surprised to learn that sometimes the two things don't go hand in hand. Today the first sample that I worked with came from Zeiss, and thus all of the names on the microscope slides were in German. While my instructor had never heard of a Maiglöckchen, if you have ever been to Germany in the spring, then you certainly have seen lily of the valley flowers. Though I have to admit that I don't know much about plant biology, the images are of the rhizome, which is the underground stem of the plant. The dyes used were a rhodamine derivative and fluorescein isothiocyanate (FITC) .

Fullerenes and the allergic response

2007-07-09T22:22:00.000-05:00

Last year I was quite intrigued when I learned that cosmetics containing fullerenes are actually already on the market, so when I noticed this paper, I decided to look it over. Everyone has heard of "bucky balls," an allotropic form of carbon named after the architect famous for building geodesic dome structures. Incorporation of C₆₀ into skin creams has been the subject of much debate; while known to be quite stable, only a handful of biological studies exist and some of them hint at the possible toxicity of fullerenes.

Interestingly, this recent study from Ryan and coworkers in the Journal of Immunology indicates that polyhydroxy C₆₀ and N-ethylpolyamine C₆₀ (water soluble "bucky balls") are capable of inhibiting the allergic response of human mast cells and peripheral blood basophils. Even though the electrons of C₆₀ are not fully delocalized throughout the entire molecule, fullerenes have long been known to be radical sponges, and it is believed that this contributes to their negative regulation of the allergic response. Mice injected with up to 250ng of fullerene showed no adverse affects, and the authors demonstrate that the concentration needed to inhibit anaphylaxis in mice is 400,000-fold lower than the dose that has been shown to be toxic in vivo. As C₆₀ is believed to reduce cellular ROS levels, it has been proposed that its antioxidant effects might be useful in the treatment of neuordegenerative diseases such as Parkinson's, Alzheimer's and Lou Gehrig's disease.

Me?? I'm just waiting for B₈₀.

Poetic Chemistry

2007-06-28T14:26:00.000-05:00

Today at the Sceptical Chymist, Catherine wrote an interesting post on poetry in the scientific literature. One of the comments contained a link to this 1971 JOC paper, which is written in quite a unique style. I suggest that you take a look.

Also, as Catherine suggested, I tried to write some chemistry/biology related haikus, and here are my attempts.

For the chemists:

Stirring at reflux
Overnight. Leaky tubing
Flooded his office

(As a side note, that didn't ever happen to me, but a post-doc in my lab managed to flood the office below his lab with some tubing that wasn't properly secured. That office luckily belonged to one of the nicest faculty members here).

For the biologists:
Oh dear western blot
where is my protein hiding?
not on the membrane

Microscopy

2007-06-26T18:01:00.000-05:00

Today was my first time trying out confocal microscopy, and I enjoyed it quite a bit. Seeing stained cells through the microscope was pretty amazing. Unfortunately the camera doesn't capture the images quite as well as the human eye, but I wanted to share one of the pictures that I captured today.

Visualization of Single Electrons

2007-06-25T18:04:00.001-05:00

Image taken from Guo, W. and Maris, H.J. Low Temp. Phys.

doi:10.1007/s10909-007-9373-2 (2007)

Yes, you can believe your eyes. The above image has captured the movement of a single electron through liquid helium, with a velocity of 6 cm/s. Researchers at Brown University have captured these traveling electrons on film in a recent Journal of Low Temperature Physics article. (You can also watch a movie on the Maris group website).

How does this work? Well, the Pauli Exclusion Principle tells us that a free electron injected into liquid helium would experience some repulsion from the atom's own bound electrons. Thus, the electrons are encapsulated by so-called "electron bubbles." Electron bubbles can't be seen under normal pressure because of their tiny size (on the order of 10^-23 cm², but utilizing soundwaves to explode and expand the electron bubbles, Guo and Maris were able to actually see the movement of electrons through a 6.8cm long helium cell that was kept at an extremely low temperature (1.3^o K which is approximately -457^o F or -272^o C). Although most of the observed bubbles traveled in a straight line, some of them followed a snakelike path, most likely following a superfluid vortex.

One question still remains--Where are these electrons coming from? As the authors point out, the liquid helium cell does not contain a source of electrons. One theory is cosmic rays might cause ionization of helium atoms, producing UV photons. As these photons hit the cell wall, it is possible that electrons could be ejected into the helium due to the photoelectric effect. A simpler explanation might be that some other kind of charged particles (such as muons) simply ionize helium atoms, producing positive and negative particles. While most of these charged particles would recombine, some might escape, allowing researchers to track their movement.

Comic Clumsiness

2007-06-19T21:13:00.000-05:00

My husband pointed out the Periodic Table of Comic Books this morning, and while I haven't had a chance to check out all of them, so far my favorite one is this Wonder Woman strip. I just love the end, where Wonder Woman says, "The hydroxo gas is transforming you into an electron and me into a proton."

Also, I thought I'd share some of my clumsiness with you. Today in Cardio Camp! I somehow managed to tear my deltoid ligament and am now restricted to hobbling around on crutches for the next few weeks. Right now I'm not sure how this will affect my labwork, but maybe I found those comic books just in time...

Top 200 Drugs...

2007-06-18T20:36:00.000-05:00

As my boss pointed out earlier this month, the Njardarson group (Cornell) currently has a listing of the 2006 top 200 generic and brand name drugs with structures. You can download the pdf files for your own pleasure or have them blown up to poster size as my group did. (The posters currently reside in our group breakroom, so that even at lunchtime, we never totally leave the realm of medicinal chemistry). It's amazing how many of the drugs that I recognized by name--and of course now it is handy to know their structure. Who knew that the estradiol analog found in many birth control pills contains an alkyne (ethinyl estradiol) that (according to wikipedia) was apparently key in creating a compound resistant to degradation by the liver? Or that the brand name drug Klor-Con (#153 on the list), which made $160,000,000 last year is actually only KCl?

Absorption of Polyphenols from Black Tea,,,

2007-06-18T20:23:00.000-05:00

Yay! According to a study in J. Agric. Food Chem., I can once again start drinking my black tea with milk.

Getting Closer to Open Access?

2007-06-13T22:09:00.000-05:00

While reading C&EN today, an advertisement promoting the ACS AuthorChoice free access option caught my eye. Maybe I am just a little behind the times, but I didn't actually know that something like this existed (and looking at the release date, it has been around almost a year). Basically, in exchange for a fixed fee (ranging from $1,000 to $3,000, paid by the author(s) or their funding agencies), the ACS allows unrestricted internet access to an author's article published in an ACS journal. This is different than the ACS Articles on Request policy which I had previously heard about; through this FREE policy, the ACS gives authors a URL that they can email out to colleagues. In this way authors can distribute up to 50 free copies of their published work, and after 12 months access to articles is unrestricted through this unique URL. Of course, Wiley journals have a similar policy (with a similar price, but limited to only the biomedical journals) called Wiley Funded Access Service.

Looking at the list of published ACS AuthorChoice Articles, I was slightly surprised to see that only 24 papers have been published in this way. Apparently the fee, while not too hefty in my opinion, prevents most authors from choosing this option. Hopefully with time, we will see more open access articles available through programs like ACS AuthorChoice and Wiley Funded Access Service. Although I like the idea of peer-reviewed open access and hope that it becomes the wave of the future, something in me says that it will be a long journey...

On a related note, these posts at In the Pipeline and Chemistry Central discuss the important role that open access journal articles play for those in the field with no literature subscription (such as the retired on unemployed).

Chemistry in my life...

2007-06-10T18:05:00.000-05:00

While reading one of my favorite non-chemistry magazines the other day, I came across the advertisement pictured above for the Lexus RX hybrid. In the closeup picture, you can see why I've decided to include it here. Whenever I see chemical information or structures in real world situations, it makes me excited that non-chemists are getting a little exposure to what I work with every day. Usually the chemistry isn't great (and sometimes it doesn't even make sense), but at least our industry is getting some recognition. Although I tried to find some connection between the structures pictured and hybrid cars, I couldn't find one. Any ideas?

Pictures from Sao Miguel

2007-06-09T20:18:00.000-05:00

My husband took most of the pictures while we were on our vacation in the Azores. While I took only about 200 pictures, he snapped approximately 1,000. He is the more advanced photographer, but it is hard to make any picture of such a beautiful landscape look bad, so most of the pictures that I took turned out pretty nicely too. Sorting through the pictures to pick out the "best" ones is difficult, but you can see a small selection below. I've left out some of the more stunning ones (taken by my better half of course), so that he will have a chance to post them himself.

Lagoa do Fogo Lagoon of Fire

Aqueduct

cliffs down to the Atlantic

São Miguel

church

baby volcano

one of the many small "ports"

I also have to add that our accommodations were absolutely wonderful: Casa Vitoriana in Ponta Delgada, Quinta das Queimadas in Nordeste, and Quinta Altamira in Caloura (near Água de Pau).

Authorship

2007-06-07T10:40:00.000-05:00

Looking through the literature, you see some papers with twenty-plus authors and others with only two or three. Maybe it is just a difference between papers coming out of industry versus those produced by academia. Sometimes I have to wonder if all twenty authors really contributed much at all to a six page paper, or maybe it is just a system of "you pat my back and I'll pat yours" (or "I'll include you on this publication if you include my name on your next one"). On the other hand, how many key people were left out of the typical two author paper? Does the undergrad who helped synthesize a key compound (through a method you carefully worked out for weeks beforehand) get left out of the author list? How about a visiting scientist that contributed ideas and demonstrated new techniques to a group? Is she kept on a publication because of the contribution of original ideas and thoughts, or do you leave her off because she didn't physically complete any of the actual experiments?

Is it enough to contribute time/manual labor? Is it enough to contribute only ideas? Or is it necessary for one to contribute both to be worthy of authorship? I've heard people say that it's only really necessary to look at the first and last author of an article, and if that's the case the debate over authorship doesn't really matter.

I'm for citing ALL of those involved in a project, no matter how small a part they played (meaning inclusion as authors, in the acknowledgments or in the references section under "personal communication"). What are your opinions?

Back from vacation

2007-06-07T10:32:00.000-05:00

I'm officially back from vacation! Expect some pictures from the Azores soon. Until then, I'll catch up on some reading ;o)

Where in the world?

2007-05-22T08:06:00.000-05:00

Well, I'm off on vacation for the next two weeks! As my better half lives in Germany, we don't get to see each other as often as we would like--we saw each other last at Christmas. This time we are going to meet "halfway." Technically, it is closer for him, but I'll take a 5 hour flight (from the east coast of the US) over a 10 hour flight any time. If there is internet access available, I will be posting updates from time to time. Otherwise expect to see pictures when I get back :o)

DNA detection

2007-05-20T13:43:00.000-05:00

Picture taken from Hammond, D.M., Manetto, A., Gierlich, J., Azov, V.A., Gramlich, P.M.E., Burley, G.A., Maul, M., Carell, T. Angew. Chem. Int. Ed. 2007, 46, 4184. 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

In my mind, the future of cancer therapy is in the hands of personalized medicine; as the genetic makeup of each patient is different, it only makes sense to utilize customized therapies depending on the mutation affecting the individual. (Just look at the story of Iressa, and how well it works for Asian nonsmoking women with mutations in the EGFR tyrosine kinase domain). While the idea is a great one, personalized therapy is not a reality yet. Currently treatment options are too limited and often unspecific; methods to detect various disease markers are lacking. Personalized medicine depends upon the detection of minute amounts of DNA as well as isolation of particular genes from biological samples of interest, and the Carell group has developed a method to help with this.

Typically PCR is used for standard DNA amplification, although newer, more sophisticated techniques have allowed for detection of DNA down to the zeptomolar 10^-21 level. (I'd never even heard of that one, my super-geeky husband had to fill me in). Unfortunately, such methods require the use of expensive/complex technology, so Carell and coworkers have developed a simple method of DNA detection based on standard black and white photography techniques. First, a pinacyanol dye was modified to contain an azide functionality, and several alkyne-containing oligodeoxyribonucleotides (ODNs) were synthesized. After a copper catalyzed Huisgen cycloaddition, various concentrations of modified ODNs were spotted down on commercial photopaper, irradiated, and developed according to known methods (standard photographic darkroom setup). This simple procedure allows for the detection of ~300 attomoles (10^-18) of DNA!

Blogging Scientists...

2007-05-16T15:00:00.000-05:00

Earlier today the paper fairy left the most recent Cell on my desk, open to the page "Scientists Enter the Blogosphere." Actually it was left on my chair, as my desk is currently a mess of papers (it's called writing a review), and I might not have seen it otherwise. There are a few people in my lab (including my boss) to whom I have casually mentioned my blog, but I'm pretty unsure if they have ever looked for it on the web. So it made me feel pretty good that my boss remembered I am a blogger.
Some fast facts from the article: Of 50 million blogs that exist, 4% of them deal with technology issues on a regular basis (20,000 of them are labeled as "science" blogs, although the term science is used loosely), 8% of internet users in the US write a blog, and only about 1000 of the science blogs out there are actually considered "authoritative."
I've been reading one of the featured blogs, In the Pipeline, for quite some time, and was thrilled when I was recently added to his blogroll. Some of the other blogs mentioned in the article that I found particularly interesting: Aetiology, The Daily Transcript, Sandwalk, and Useful Chemistry.
On a slightly related note, this recent post by Excimer (and all of the commenters there, especially Chembark) really got me thinking--Do blogs already serve as an unofficial review/comment system for scientific articles?

Going Decaf...

2007-05-13T19:22:00.000-05:00

Several months ago, Justin P. Gallivan gave quite an entertaining seminar for the chemical biology department. While I'm officially a member of the organic division, I really enjoy the biological side of things, so I try to attend these seminars as often as possible (or sometimes I attend them when my boss sends out an email "please attend," which really means "required seminar"). If I remember correctly, Prof. Gallivan did a little "bacteria dance," and if a speaker goes that far to get our attention, he has my respect :o) His lab actually has done some extremely interesting work, and I've been waiting for a publication to come out ever since that seminar.

Last week, the article "Guiding Bacteria with Small Molecules and RNA" finally appeared in JACS. E. coli have 5 chemoreceptor proteins and thus can maneuver their way through complex chemical environments. While they naturally perform chemotaxis toward 30+ compounds, it would be useful in terms of bio-nanotechnology to reprogram these bacteria to respond to new and unique chemical signals. The pathway responsible for converting chemical ligand binding into a change in direction of the bacteria consists of 6 chemotaxis proteins, with the protein known as CheZ ultimately responsible for bacterial motility. With this in mind, Shana Topp from the Gallivan group created a theophylline-sensitive synthetic riboswitch to control translation of CheZ; without theophylline, the conformation of mRNA prevents translation of CheZ, forcing the bacteria to tumble in place. Once theophylline is added to the mixture, the mRNA adapts a different conformation in which the ribosome binding site is open, which allows for expression of CheZ and forward movement of the bacterial cells. Caffeine, which has a structure similar to that of theophylline, did not elicit a response from bacteria, indicating that the observed changes in bacterial motiliy are dependent on the riboswitch. As Topp and Gallivan jokingly state, "E. coli pick decaf!"

Nucleophilicities of Amines in Water

2007-05-09T13:46:00.000-05:00

A lab-mate alerted me to this article in the current issue of JOC, and if you are at all interested in comparing the nucleophilicities of amines, then it is worth taking a look. In the past, nucleophilicity has been measured by investigating the kinetics of nucleophilic additions and substitutions. For instance, the rate of reaction of primary or secondary amines with CH₃I/CH₃Br or stabilized carbocations can be measured and directly related to nucloephilicity using a general formula:Bunting [1, 2] and coworkers have characterized the nucleophilicities of over 70 amines to date using a variation of this method (reactivity towards 1-methyl-4-vinylpyridinium cation as well as methyl 4-nitrobenzenesulfonate).

More recently, researchers from the Mayr lab have utilized benzhydrylium ions (electrophiles) to study the nucleophilicity of various non-amine nucleophiles; as it would be useful to have methods for comparing nitrogen bases in order to design new organocatalytic reactions, they have expanded these methods to include 26 amines. While many of the observations are completely logical (increased branching decreases the nucleophilicity of primary amines, ammonia is less nucleophilic than methyl amine which is less nucleophilic than dimethylamine--which tracks nicely with basicity), others were quite unexpected (at least for me, and I'm certainly not an expert). According to this research, aniline, which is quite a bit less basic than ammonia, is a much stronger nucleophile than ammonia.

As chemists, we all know that basicity certainly doesn't equal nucleophilicity, but this article really drives that fact home.

Update: Thanks to Handles for pointing out this website where Mayr has put all of the nucleophilicity data online :o)

Random observation

2007-05-07T20:05:00.000-05:00

Why does it disturb me so much that chemistry.com is not a chemistry website at all, but an online dating community? That is just wrong.

Aliens

2007-05-04T18:29:00.000-05:00

Well, this last week has been a hard one--Fortunately I'm far enough along in my graduate career that I don't have to deal with the stress of final exams, but my body decided to play tricks on me anyway. After dealing with the stomach flu last week, this week I've been suffering from a head/neckache. Since I'd had it for over 5 days, I decided to go to the student health center, which was a big mistake--for some reason, they thought I had meningitis (Normally I would put a wikipedia link there, but the picture that came up when I did that made me sick to my stomach, so today I'll leave the link out), and they sent me to the emergency room. The doctors there assured me that I was only suffering from a muscle spasm in my neck, gave me some pain killers, and left me with a hefty bill to pay. When they can't tell the difference between muscular pain and a deadly illness, I start to doubt the effectiveness of the university health care system....So that explains why my post today will be relatively light :o)

If you're like me, when you think of aliens, you think of little green men with saucer shaped eyes and strange metallic clothing. Why do we always imagine aliens to be green--Is this really an accurate representation of animals or plants in other solar systems? Well after a lengthy review of photosynthesis on Earth, researchers at Rice University, Washington University, UIUC, and NASA have come up with a set of rules for predicting what colors might be photosynthetically relevant on other planets. Photosynthetic pigments evolve over time in sync with the atmosphere of a planet and the characteristics of its parent star; it is proposed that they have peak absorbance at the blue and red ends of the atmospheric transmittance window for light harvesting, as well as at the wavelength of peak incident photon flux. Thus, if we know the patterns of incident radiation for other stars, we can begin to predict what kind of photosynthetic machinery might be necessary on those planets, as well as the color of these photosynthetic pigments. So we can basically predict what color the trees might be on Jupiter.

Cool, huh?

I first read about these articles on heise.de, but a nice summary can also be found here on the Goddard Institute for Space Studies (part of NASA) website, with reprints of the two Astrobiology papers here and here.

Space, the final frontier...

2007-04-30T15:01:00.000-05:00

With a great title like"Chemical Space Travel" I just couldn't pass up this early view article in ChemMedChem. Though I'm not sure that I totally buy into this as a method for discovering new drugs, it is an interesting concept nonetheless. Currently, it is estimated that there are 10²⁰ to 10²⁰⁰ "drugable" organic molecules. As it is impossible sift through all of these structures when searching for new lead compounds, knowing what region of chemical space to explore beforehand might be beneficial. Thus, researchers in the Reymond group at the University of Berne in Switzerland have developed a computer program that serves as a "spaceship" for chemical space travel; a point mutation generator serves as a "propulsion device," and a similarity score serves as a "compass." In simpler terms, starting from any molecular structure "A", this program first completes one of eight possible mutations on each atom/bond in the molecule: atom exchange, atom inversion, atom removal, atom addition, bond saturation, bond unsaturation, bond rearrangement, or aromatic ring addition. Then, the similarity between each mutant and the target compound "B" is measured. The 10 mutants that are most similar to the target "B" and 20 random mutant molecules are carried on for another round of mutation/selection. This continues on until one arrives at the target molecule "B," and along the way thousands of unique structures are generated.

One easy example is illustrated below: Starting from methane, 12 mutations produced cubane--but along the way 6638 unique compounds were generated, taking the 10 most similar to the target (in this case cubane) and 20 random compounds at each mutation step. All compounds that were unstable or not synthetically feasible were eliminated. In the same fashion, from cubane to methanol, there were only 7 steps necessary, and during the process almost 1000 new molecules were generated.

So how could this be used for drug discovery? Well, to do this, the authors investigated the chemical space between AMPA and CNQX (shown below); both are known to be agonists of the AMPA receptor, which is a glutamate receptor in the central nervous system. Using these two compounds, over 559,656 compounds were obtained after after 500 runs, which created this cool looking graph. Colors for the graphs are as follows: AMPA to CNQX, in green; CNQX to AMPA in blue, run-away compounds in gray, AMPA to CNQX mutant series in orange, CNQX to AMPA mutant series in pink, and in red are the best docking compounds--or in other words compounds that actually are predicted to bind into the active site of the AMPA receptor (this was determined through computational docking studies). If you haven't noticed, the novel inhibitor with the best predicted affinity for the AMPA receptor is a combination of an amino acid group from AMPA and an aromatic group originating from CNQX.

Image taken from ChemMedChem 2(5), 636.

So the next time you are looking for novel chemical inhibitors, why don't you just take a ride in a chemical spaceship...

Fair use?

2007-04-26T21:23:00.000-05:00

I just read about this over on Chemistry Central. Basically, a graduate student blogger at the University of Michigan was threatened with legal action for using some copyrighted figures in her blog. Fortunately the matter has been resolved, but it still opens up the question: What is fair use?

Anyway, I'd almost prefer an email like that over this kind of unpleasantness. I guess I'm lucky that my boss is a nice guy.

Chemistry and......Sports???

2007-04-25T13:24:00.000-05:00

Imagine my surprise this morning when I took a peek at the sports section of the daily newspaper here on campus:

The article doesn't have anything to do with chemistry (you can read it here if you are interested), but I still thought it was cool to see a periodic table on the front page of the sports section. All press is good press, right?

Aggravating Aggregation

2007-04-23T15:43:00.000-05:00

Anyone interested in the field of high-throughput screening shouldn't miss this article which appeared online in the ASAP section of J. Med. Chem last week. Generally medicinal chemists can avoid false positives in screens by utilizing the well known Lipinski's Rule of Five or other computational methods that identify potential problematic molecules. Unfortunately, compounds that form colloidal aggregates are particularly troublesome; through sequestration of an enzyme from its substrate, these molecules usually appear to be good inhibitors (with IC50 values as low as 1 micromolar) with rather steep dose response curves. As aggregate-based inhibition is abrogated through the use of moderate concentrations of non-ionic detergents such as Triton X-100 (0.01 to 0.1%), Feng and coworkers developed an assay to test 70,563 compounds for detergent-sensitive inhibition. This screen has really opened my eyes to the prevalence of aggregators among screening hits. Astonishingly, of 1274 beta-lactamase inhibitors identified, 1204 were detergent sensitive, indicating an aggregation based mechanism of inhibition for 1.7% of the library! Anyone that has sorted through thousands or hundreds of initial hits will see the advantage of being able to identify or eliminate these artifacts from screens.

Discovering that a molecule is an aggregator is not a death sentence for its future use; as aggregation is concentration and condition dependent, molecules known to aggregate in one screen might not in a different setting. Additionally, several known drugs are aggregators at concentrations below 100 micromolar, including clotrimazole, nicardipine, delavirdine, and benzyl benzoate as pointed out by this 2003 article in J. Med. Chem.

Janus Disks

2007-04-19T16:40:00.000-05:00

What exactly is a Janus disk? Well, with a quick internet search you can easily find several references to Janus, the Roman god of doorways, gates, and beginnings (hence the word January for the first month of the year), but a picture search is actually most revealing. Usually Janus is shown with two different faces that look in opposite directions; one represents the sun and the other symbolizes the moon. Interesting--but what does this have to do with chemistry??

Well after that brief review of Roman mythology, one can easily imagine that a Janus particle is composed of two fused hemispheres of different materials--similar to the bust of Janus pictured above. Depending on their actual shape, Janus particles are placed into three categories: spheres, disks and cylinders. Several potential applications of these two-sided particles have been envisioned. For instance, in solar cells two very different types of molecules (donors and acceptors) must work together and convert light into electron movement; thus, using Janus particles within light harvesting devices might increase solar cell efficiencies. One could also imagine a Janus-scaffold as a drug delivery system; half of the disk might target cancer cells, while the other end would deliver a cytotoxic drug.

Synthesis of Janus structures is a daunting task and only a few examples of non-spherical Janus particles exist in the literature; thus, when I came across this article in JACS today, it caught my attention. Researchers at the University of Bayreuth in Germany have recently succeeded in producing Janus disks utilizing a template-assisted synthesis. Polymers made of polystyrene-block-polybutadiene-block-poly(tert-butyl methacrylate) were self-assembled and then treated with either AIBN or S2Cl2 to crosslink the inner polybutadiene layer; this step preserves the orientation of the polystyrene and poly(tert-butyl methacrylate). Finally, after sonication the Janus disks are obtained in their final form; size of the disks is tunable and ranges from the micro- to nanometer scale. As Janus structures have also been proposed to have potential as surfactants, the effect of these Janus disks on the interfacial tension of liquid-liquid interfaces was studied as well. Compared to their un-crosslinked starting materials, the Janus disks have a remarkable ability to decrease interfacial tension, and therefore future technological applications might include the stabilization of emulsions or encapsulation of molecules.

Picture taken from http://dx.doi.org/10.1021/ja068153v

I want one...

2007-04-18T19:18:00.000-05:00

A few days ago jungfreudlich posted pictures of his Element Collection. Very cool, don't you think? You can buy them online here, but probably not on a graduate student's salary :o)

Impact factors

2007-04-16T20:00:00.000-05:00

Have you ever taken a few seconds to explore the impact factors of your favorite journals? If you've never done it before, I highly recommend taking a closer look at the ISI Web of Knowledge, especially the Journal Citation Reports (JCR). Whether or not you believe impact factors doesn't really matter--it's pretty interesting nonetheless.

For instance, the first article ever published with my name on it was in Organic Letters, which has an impact factor of 4.368 according to JCR. More recently, some of my work could be read in the international edition of Angewandte Chemie--impact factor 9.596. Does this mean I am slowly moving up the ladder of scientific respect? Well, there is actually a lot of debate about this subject, and some people believe that journal impact factors don't accurately represent the real importance of journals; would it be better to just use actual article citation numbers?

Before I move on, I think it is pretty important to understand how impact factor is calculated. Here is what goes into an impact factor calculation:

Using Angewandte Chemie International Edition as a real life example--in 2005 there were 11384 other articles citing articles from the year 2004, and 10620 other articles citing articles from the year 2003, for a grand total of 22004 citations. Divide this by the total number of articles published in 2003 and 2004 (2293) to get 9.596, the impact factor. Pretty simple, right? Well, the JCR reports a number of other interesting factors including the immediacy index (number of cites to "current" articles divided by number of current articles), journal cited half life (the median age of articles that are cited in the current year), and several graphs that condense some of this information.

Does the impact factor really measure the quality of a journal (or the importance of the articles published in the journal)? Well, it is true that some of the journals that I consider to be the best in the field have some of the highest impact factors. On the other hand, it's important to keep in mind that these numbers also reflect the latest trends in the literature. Availability of journals can be an issue, along with the amount of current interest and publication in a particular area.

Below is a condensed list of my favorite journals and their 2005 JCR impact factors:

Protein folding

2007-04-13T21:33:00.001-05:00

Another interesting link that my husband recently pointed out:

Folding@Home project (FAH)

Basically, using a technique called "distributed computing," researchers in the Pande group at Stanford hope to better understand protein folding and mis-folding. This of course is a noble cause, as incorrect protein folding or aggregation might be responsible for a variety of disease states; Alzheimer's, Huntington's, Parkinson's, and the big one--cancer (as related to p53)--have all been linked to protein misbehavior. Instead of using a supercomputer for all of these protein folding calculations, FAH relies on people like us to download and run software devoted to their cause. While there are almost 200,000 active CPUs in FAH, a typical supercomputer has only 5000. So far FAH has been quite successful, as of March 21, 2007 over 40 publications have been attributed to FAH calculations.

Would you be willing to donate your computer's down time to a good cause?

Gypsum megacrystals

2007-04-11T18:52:00.000-05:00

picture taken from Garcia-Ruiz, J.M. et al. 2007 Geology 35(4), 327.

Although this isn't exactly a chemistry article, it is most certainly chemistry related, and I hope that you will agree that these pictures are too awesome to believe. The gigantic crystals pictured above made the cover of this month's Geology. Almost 80 years ago, the excavation of caves and tunnels at the Naica mine (112km Southeast of Chihuahua, Mexico) led to the discovery of meter-sized single crystals of selenite, which is one of the four crystal forms of gypsum. (The other three forms are satin spar, desert rose, and gypsum flower. As a side note, when I was younger I had a great collection of rocks and minerals that included a very nice sample of desert rose). Often these crystals of calcium sulfate dihydrate are found coated in calcite (calcium carbonate), celestite (strontium sulfate), or trace amounts of iron oxide, which give the crystals either a white or slightly red hue; selenite is colorless/transparent in its pure form. Amazingly, the Cueva de los Cristales (Cave of Crystals) contains selenite crystals up to 11 meters in length and 1 meter thick, with minimal contamination from other minerals.

While several have made conjectures as to how these crystals formed, none had been investigated carefully until now. Garcia-Ruiz and coworkers set out to explain the formation and growth of the Naica megacrystals after closely considering several factors. First, gypsum is slightly soluble in water, with a maximal solubility observed at 58 degrees C; conveniently, water samples from the Naica mines have temperatures ranging from 48-59 degrees C. Thus, the water found in the area is slightly supersaturated for gypsum and slightly undersaturated for the anhydrite form of calcium sulfate, suggesting a self-feeding mechanism. In other words, crystal growth might have been driven by a solution controlled anhydrite-gypsum phase transition. Calculation of the nucleation rate indicated that this suggested mechanism is a probable one, but only within a very narrow range of temperatures--46 to 60 degrees C. Such calculations indicate that these crystals have been growing in the caves at Naica for over one million years!

For more information:

The Largest Crystals on Earth

More pictures

Photovoltaic devices from viruses

2007-04-08T21:27:00.000-05:00

Viral capsids are attractive scaffolds for the preparation of nanomaterials; they are highly robust in nature, monodisperse, easy to assemble, and small in size. In particular, the hollow tube-like capsid of the tobacco mosaic virus (TMV) provides an intriguing template for the development of organic nanowires. When fully assembled, each TMV particle is 300nm in length and is made up of over 2000 identical protein subunits that can be assembled into other aggregate structures; depending on pH and ionic strength conditions during assembly.

Thus, the idea to create light-harvesting systems out of assembled TMV capsids is not a surprising one. In fact, in the literature numerous methods have been developed to modify both the interior and exterior of the viral capsid with inorganic substrates,[1,2,3] but little success has been as been achieved with organic ones. So you can imagine that I was especially excited when I saw the title "Self-Assembling Light-Harvesting Systems from Synthetically Modified Tobacco Mosaic Virus Coat Proteins" in JACS quite recently. Ever since Prof. Matthew Francis gave a seminar here, I've had his group website bookmarked and have been watching for new developments.

In nature, sunlight is converted into chemical bonds with a high efficiency, mostly due to the fact that photosynthetic systems incorporate several types of chromophores (covering a large spectral bandwidth) spaced precisely to optimize energy transfer. In an attempt to mimic the ingenuity of nature, Miller and coworkers utilized a mutant TMV monomer bearing a reactive cysteine residue. At pH 7 in a phosphate buffer, this reactive cysteine was coupled with maleimide functionalized Oregon Green (primary donor), tetramethylrhodamine (secondary acceptor), or Alexa Fluor 594 (acceptor). In order for this to work, FRET must occur between the selected donors and acceptor, and these dyes were chosen for their high degree of overlap in the solar spectrum as well as their high extinction coefficients and stability. By mixing various ratios of donor and acceptor monomers together and then adjusting ionic strength and pH, both disk and long rod aggregate structures were formed; the attached chromophores apparently had no effect on the systems ability to self assemble. A ratio of 33:1 (donor Oregon green) to acceptor (Alexa Fluor 594) produced an overall efficiency of 47%, while the 3-chromophore system containing 8:4:1 Oregon green: tetramethylrhodamine: Alexa Fluor 594 resulted in a stunning 90% efficiency!

Though it is a simple concept, the combination of self-assembling biological scaffolds and synthetic organic chromophores seems to have great potential for the development of new solar cells.

Organometallics, the final frontier?

2007-04-05T18:44:00.000-05:00

For the past few months I've been following the work coming out of the Meggers lab at the University of Pennsylvania. A nice summary of their ruthenium based protein kinase inhibitors was recently published in Synlett [1], and while I'm certainly a little rusty on organometallic chemistry, I find their approach fascinating nonetheless.

Exploring chemical space with organometallics makes complete sense; carbon-based molecules can only form linear, trigonal planar, or tetrahedral geometries, so why not explore elements that are pentavalent or hexavalent and can thus form unique bioactive scaffolds? In a recent lecture, Meggers pointed out that an asymmetric tetrahedral carbon can form 2 stereoisomers, but an octahedral center with six substituents can form 30 different stereoisomers. (For those non-believers, Meggers had actually drawn out all 30 different stereoisomers on a slide).

In their search for a octahedral carbon-substitute, Meggers and coworkers concentrated on ruthenium because of its low cost, low toxicity (in the II and III oxidation states), high stability, and synthetic tractability. Using the ATP-competitive protein kinase inhibitor staurosporine as the basis for a ruthenium ligand, a small library of complexes was synthesized (100 members total, with 12 different ligands overall). Screening against several kinases revealed that several of the ruthenium based inhibitors were quite potent, with IC50 values in the nanomolar range. What I find most amazing is the fact that the staurosporine-based pyridocarbazole ligand is 19,000 times less potent than the ruthenium complex containing the same ligand. Further application of this strategy has led to the discovery of highly selective protein kinase inhibitors (for Pim-1, GSK-3, MSK-1), some with picomolar binding constants. A crystal structure confirmed the initial hypothesis that the ruthenium center is not involved in any direct interactions with the protein; the metal center works to orient the organic ligands in a conformation that favors binding.

Reactions that work

2007-04-03T18:28:00.000-05:00

Looking for a way to prepare nucleoside-5'-carboxylic acids? Then I have just the reaction for you. Using a procedure adapted from Epp and Widlanski [1], one can easily make these carboxylic acids in just under three hours. In my hands, this reaction has worked wonderfully every single time, producing relatively pure product without much effort on my part; over the years it has become one of my favorite reactions.

Here is a sample procedure, exactly as it appears in my lab notebook:

Place 5g of acetonide protected adenosine in a 100ml round bottom flask. Add stir bar, 11.53g of DIB and 0.51g of TEMPO. Add 15ml of acetonitrile to 15ml of water and add to the reaction flask. Stir. After about 15 minutes the the reaction will turns a deep brown-orange color and the components begin to dissolve. Shortly after this a white precipitate forms. Stir for an additional 3 hours. Filter the solid and triturate sequentially with acetone and diethyl ether (3x each, 15ml). Dry the resulting solid under vacuum. No further purification necessary.

Yield: 4.98g, 96.8%

Large or small scale, the yield for this reaction is usually in the 90% range.

Bioethics and DCA

2007-04-02T20:06:00.000-05:00

Earlier this week I got an email from a boy in China, asking me to send him a compound that was synthesized by one of my lab-mates and was subsequently shown to kill cancer cells. At first I thought the email was spam, but after closer inspection I realized that it wasn't; he wasn't well informed, but had obviously read an article related to our lab's work and wanted the compound to give to his mother. Unfortunately, because this drug is still in pre-clinical phase my lab can't do anything to help cancer patients like this Chinese boy's mother. I felt awful and didn't know what an appropriate response would be to his email.

Anways, this relates to an article that I read at the end of this week entitled "Cancer patients opt for unapproved drug." It was pretty fascinating and made me think. Basically, in January, Bonnet and coworkers [1] at the University of Alberta demonstrated that the small molecule dichloroacetate (DCA) can force cancer cells to undergo apoptosis and decrease tumor growth with limited toxicity. It sounds too good to be true, but the science behind it makes sense. Cancer cells have a unique metabolic profile, as the glucose oxidation that normally takes place in the mitochondria is not functional; thus, the mitochondria is considered "inactive" and the cells rely on cytoplasmic aerobic glycolysis for energy production. As a result of this mitochondrial damage, tumors have increased glucose uptake and metabolism, and this is considered one of the better markers of cancer cells. Studies have shown that several human cancers cell lines have hyperpolarized mitochondria and reduced oxidative metabolism; through inhibition of the mitochondrial enzyme pyruvate dehydrogenase kinase (PDK), DCA is able to reverse these changes to the mitochondria, which in turn allows tumor cells to be killed through apoptosis. Most amazingly, tumor volumes were reduced in of nude rats that drank DCA dissolved in drinking water and no toxicity was observed. As DCA has been used in clinical trials for the treatment of mitochondrial diseases and has a patented structure, big pharma wasn't interested in developing it as a drug.

This is where things start to get a little more interesting. After a little research on DCA, Jim Tassano, the owner of a pest control company in California, teamed up with chemist Joseph Ryan to make DCA. After they came up with a suitable synthesis, he set up two websites: one is devoted to selling this homemade DCA for veterinary use, and the other provides contains excerpts from the Bonnet paper as well as a DCA discussion forum with over 1,000 posted messages. Although the FDA has not approved of the use of DCA in humans, many of the posts on the forum are from cancer patients taking DCA and reporting on its effectiveness, a "clinical trial" of sorts. Researchers are worried that these patients are not only endangering themselves by taking an unapproved drug, but also hindering attempts of completing a real clinical trial. Approximately 95% of cancer drugs in clinical trials don't get approved for human use, usually due to ineffectiveness or undesirable side effects. Sadly many patients don't have time to wait for clinical trials to be completed, and therefore they are willing to subject themselves to the unknown in hopes of beating cancer.

I certainly see both sides of the issue. While the chemist in me cringes at the thought of ingesting any non-pharmaceutical grade chemical (the website that sells DCA claims a purity of more than 99%, with impurities of 0.5% monochloroacetic acid and/or trichloroacetic acid, which doesn't come close to the purity requirements for pharmaceuticals), my compassionate side wants to offer a ray of hope to those suffering.

Alphabet Soup

2007-03-28T21:37:00.000-06:00

Image from Carlos J. Hernandez/Thomas G. Mason, UCLA Chemistry. This image is published in the Journal of Physical Chemistry C.

"Colloidal Alphabet Soup: Monodisperse Dispersions of Shape-Designed LithoParticles" by the Mason group at UCLA is the cover article for the Journal of Physical Chemistry C this week. Although this article was brought to my attention by my husband (a physical chemist of course), I found it interesting nonetheless. Taking advantage of high-throughput automated stepper lithography, graduate student Hernandez literally generated a soup of three-dimensional colloidal particles--including letters of the alphabet, crosses capable of alignment and formation of columnar structures, donut particles that can aggregate to form tubes as well as various combinations of the above. Lithioparticles, as the authors call these miniature polymeric colloids, range in size from micron to submicron units and can be colored through the incorporation of green, red, or blue fluorescent dyes.

So what exactly is "stepper lithography"? First, both a sacrificial layer and a polymeric photoresist layer are placed on top of a silicon wafer through a process known as spin coating. Using the "stepper," or a fully automated lithiographic projection exposure system, UV light is shined through a stencil-like "mask"and through the stepper's lens onto the photoresist layer. This step crosslinks the part of the photoresist that was exposed to UV light (the part not covered by the "mask"). Exposure to an organic developing solvent removes the unexposed photoresist, while leaving behind both the sacrificial layer and crosslinked LithoParticles. Finally the sacrificial layer is dissolved in water, and the alphabet soup is lifted off the surface of the silicon wafer into an aqueous solution. Once they are in solution, the particles are relatively stable, and the aqueous solvent can be exchanged for something organic.

For me the final paragraphs of the article were the most exciting part to read, as the authors discussed possible applications of designed Lithoparticles. By incorporating fluorescent molecules or other probes such as DNA or charged molecules, Lithioparticles might be useful for studying microstructures inside of cells. Tiny tweezers made out of lasers can be used to move letters of the "alphabet soup," (which is nicely illustrated by the UCLA below) and in this fashion cells could be identified with a unique symbol. Could it be possible to use this technology to mark cancer cells with a "X" and thus facilitate their elimination?

Well, with this technology, that dream might be one step closer to reality.

DOI: 10.1021/jp0672095

DNA

2007-03-27T20:50:00.000-06:00

Read my VisualDNA™ Get your own VisualDNA™

Review: Molecular Modeling Kits

2007-03-26T21:17:00.000-06:00

Check out this review of 4 of the most common molecular modeling kits out there (in German):

Molecular Modeling Kits

As a chemist can never have too many molecule building kits, I actually own kits number 1, 2, & 4 as they are presented in the link.

Beware of the Portugese Man-of-War

2007-03-26T19:47:00.000-06:00

Since I'll be traveling at the end of this week (unfortunately not to the ACS meeting), I decided to post something relevant to my destination. According to the people I'm visiting, there is currently an infestation of Portugese Men-of-War on the beaches and in the surrounding water of this sunny locale. As I consider myself equal parts organic chemist and chemical biologist, I thought that this might make for an informative post. Interestingly, the Portugese Man-of-War is a siphonophora; thus, it is a colonial species, made up of four different types of polyps. While each is an individual, they are completely integrated with each other and the colony is often mistaken for one large jellyfish. Its tentacles can be up to 50 meters long! Although I couldn't find much information about the chemical composition of Physalia physalis venom, I did learn that it consists of ATPase, RNase, AMPase, and nonspecific aminoesterases [1], most of which work to degrade cellular content, producing extreme pain in the process. 28% of the venom protein consists of physalitoxin, which is a large heterotrimeric glycoprotein that hemolyses mammalian erythrocytes. Cells treated with man-of-war poison generally release histamine. Research has shown that the venom itself creates pores in the cell membrane, allowing for the free transport of mono- and divalent cations [2], which has a major impact on the cardiac system of poisoned animals. Usually man-of-war stings are not fatal to humans, unless one is stung while swimming in extremely deep water. According to many websites, treatment with either hot or cold water best relieves pain from stings, while vinegar may cause the tentacles to release more venom, and should be avoided.

Also, I shouldn't fail to mention that Richet won the Nobel Prize for his work with the Portugese Man-of-War, in which he discovered and characterized anaphylaxis (an extreme allergic reaction).

Can anyone guess where I am headed?

photo taken from: Lilactree

Mechanophores: a force to be reckoned with

2007-03-23T20:12:00.000-06:00

The concept is logical and easy to follow--if reactions can be triggered by light, heat, pressure, or electrical potential, then why can't mechanical force also be harnessed to distort molecules in a way that promotes reaction? Actually, using molecules appropriately termed mechanophores, the Moore group has succeeded in employing the mechanical forces generated from ultrasound to promote and influence chemical reaction pathways. Although ultrasound generally has no effect on small molecules, the collapse of cavitation bubbles produced during sonication can agitate polymers in solution, generating friction, otherwise known as mechanical force. By incorporating small molecule mechanophores (either trans- or cis-1,2- dimethoxybenzocyclobutenes, BCBs) into a larger polymer, researchers were able to take advantage of this force and promote ring opening. According to the Woodward-Hoffmann rules, in a reaction promoted through light energy, both cis- and trans- BCBs undergo a disrotatory ring opening, while thermal activation produces conrotatory products. On the other hand, computational studies indicated that under mechanical influences, the cis-BCB would produce the disrotatory product, but the trans-BSB would generate the conrotatory product.

In order to test this hypothesis, the BCB-containing polymer was sonicated at 6-9 degrees C with an excess of a pyrene functionalized maleimide, which was meant to function as a a dienophile trap. Indeed, the mechanophore did behave as predicted; by distorting bond lengths and angles sonication produced the trans-BCB through a conrotatory process, while the mechanical force worked to reduce the energy barrier for a disrotatory reaction pathway for the cis-BCB. As the article title indicates, reactions can certainly be biased through the use of mechanical force.

So what will the next mechanophore be?

doi:10.1038/nature05681

2007-03-22T20:18:00.000-06:00

Earlier this week I saw a list of "10 suggestions for becoming a more pretentious graduate student." As much as we hate to admit it, chemists can be a little overbearing at times, and this list just describes graduate school struggles soooo accurately. I thought it was hilarious, so I wanted to share it:

http://blog.everydayscientist.com/?p=434

	First complimenting you on a past accomplishment and then saying "Gee, it would be great if you could do something like that again..."
	Public Humiliation
	Setting realistic goals together with you in a one-on-one meeting
	Scolding you like a small child.
	He doesn't motivate me. Ever.
	All of the above